Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism.

Leibovich, Samuel; Polverini, Peter J.; Fong, Tim; Harlow, Lisa A.; Koch, Alisa E.

doi:10.1073/pnas.91.10.4190

Cited by 177 publications

(99 citation statements)

References 40 publications

(60 reference statements)

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“…7) (6,17,18). Le y g stimulated chemotaxis of HMVECs at concentrations from 10 pM to 1 mM, inducing migration equivalent to 60 nM control angiogenic bFGF (Fig.…”

Section: Ec Chemotaxis Induced By Le Y /Hmentioning

confidence: 99%

Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

Halloran

Carley

Polverini

et al. 2000

The Journal of Immunology

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Endothelial cells (ECs) are key participants in angiogenic processes that characterize tumor growth, wound repair, and inflammatory diseases, such as human rheumatoid arthritis (RA). We and others have shown that EC molecules, such as soluble E-selectin, mediate angiogenesis. Here we describe an EC molecule, Lewisy-6/H-5-2 glycoconjugate (Ley/H), that shares some structural features with the soluble E-selectin ligand, sialyl Lewisx (sialyl Lex). One of the main previously recognized functions of Lewisy is as a blood group glycoconjugate. Here we show that Ley/H is rapidly cytokine inducible, up-regulated in RA synovial tissue, where it is cell-bound, and up-regulated in the soluble form in angiogenic RA compared with nonangiogenic osteoarthritic joint fluid. Soluble Ley/H also has a novel function, for it is a potent angiogenic mediator in both in vitro and in vivo bioassays. These results suggest a novel paradigm of soluble blood group Ags as mediators of angiogenic responses and suggest new targets for therapy of diseases, such as RA, that are characterized by persistent neovascularization.

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“…7) (6,17,18). Le y g stimulated chemotaxis of HMVECs at concentrations from 10 pM to 1 mM, inducing migration equivalent to 60 nM control angiogenic bFGF (Fig.…”

Section: Ec Chemotaxis Induced By Le Y /Hmentioning

confidence: 99%

Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

Halloran

Carley

Polverini

et al. 2000

The Journal of Immunology

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“…Indeed, there is emerging evidence that NO release serves as a prerequisite for epithelial and endothelial cell motility (11)(12)(13). Leibovich et al (13) have shown that production of angiogenic activity by activated monocytes (assayed by chemotaxis of endothelial cells and corneal angiogenesis) is absolutely dependent on L-arginine and NO synthase.…”

mentioning

confidence: 99%

Permissive Role of Nitric Oxide in Endothelin-induced Migration of Endothelial Cells

Noiri

Bahou

et al. 1997

Journal of Biological Chemistry

151

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Endothelin (ET) synthesis is enhanced at sites of ischemia or in injured vessels. The purpose of this study was to explore the possibility of autocrine stimulation of endothelial cell migration by members of the endothelin family. Experiments with microvascular endothelial cell transmigration in a Boyden chemotactic apparatus showed that endothelins 1 and 3, as well as a selective agonist of ET B receptor IRL-1620, equipotently stimulated migration. Endothelial cell migration was unaffected by the blockade of ET A receptor, but it was inhibited by ET B receptor antagonism. Based on our previous demonstration of signaling from the occupied ET B receptor to constitutive nitric oxide (NO) synthase (Tsukahara, H., Ende, H., Magazine, H. I., Bahou, W. Formation of new blood vessels, driven by the morphogenetic program and/or by the functional demand for increased blood supply, is initiated by the budding of endothelial cells off the microcirculatory bed. Tissue hypoxia represents a physiologic stimulus for angiogenesis, and several autocrine angiogenic mediators produced by endothelial cells have been recognized (1-3). Endothelin, one of such mediators, is constitutively produced by endothelial cells and its production is enhanced by hypoxia (4 -6). Two investigative teams have recently demonstrated that ET-1 1 and ET-3, acting via the ET B receptor, stimulate endothelial cell migration and proliferation (7, 8).Since we and others have previously demonstrated that occupancy of ET B receptors in endothelial cells is accompanied by the activation of constitutive endothelial NO synthase (9, 10), we hypothesized that the observed motogenic effects of members of the ET family may in fact be mediated by the release of NO. Indeed, there is emerging evidence that NO release serves as a prerequisite for epithelial and endothelial cell motility (11-13). Leibovich et al. (13) have shown that production of angiogenic activity by activated monocytes (assayed by chemotaxis of endothelial cells and corneal angiogenesis) is absolutely dependent on L-arginine and NO synthase. These observations are in concert with findings reported by Ziche et al. (12) who detected the potentiation by sodium nitroprusside of the angiogenic effect of substance P in the rabbit cornea. Our own observations expand this function to the classical angiogenic signal, vascular endothelial growth factor. We demonstrated that endogenous NO production by the endothelial cells is a prerequisite for the motogenic and angiogenic effects of this factor.2 In the present study, we used three different approaches (migration and wound healing by endothelial cells, wound healing by Chinese hamster ovary cells expressing ET B receptor with or without eNOS, and application of antisense oligodeoxynucleotides targeting eNOS) to provide evidence that the effect of ET-1 on cell migration is mediated via ET B receptor and requires functional enzymatic machinery for NO generation. MATERIALS AND METHODSCell Culture and Reagents-Renal microvascular endothelial cells (RMVEC) were...

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“…Nitric oxide has been demonstrated to contribute to angiogenesis 22,31,32 and cyclooxygenase-2 (COX2) induction by mechanical stimuli. 39 Vascular endothelial growths factor and COX2 have been noted to be induced in this overexercise animal model.…”

Section: Discussionmentioning

confidence: 99%

“…20,22 On the other hand, there is a growing body of evidence that suggests that NO is important in the healing of soft tissues including gastric ulcers, 23 anal fissures, 24 tendon, 25,26 skin, 27,28 and bone. 29,30 Furthermore, NO promotes processes crucial to wound healing such as angiogenesis, 31,32 cell proliferation, 33,34 and collagen synthesis. 27,28 In an acutely injured tendon-healing animal model a temporal and differential expression of all three NOS isoforms has been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of nitric oxide synthases in tendon overuse

BENDERL

ULUKAPI²,

BALKANLI

et al. 2005

Journal Orthopaedic Research

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Tendon disorders with a chronic nature, including the rotator cuff, are extremely common, and represent a major clinical problem. Mechanical overload has been proposed as an important etiologic factor in tendinopathies. Nitric oxide (NO), a free radical produced by nitric oxide synthases (NOSs), is a potent regulator and stimulator of biological processes including tendon degeneration and healing. It is also involved in response to mechanical stimuli in different tissues. In an animal model of acutely injured tendon healing temporal and differential expression of NOS isoforms has been demonstrated, suggesting that different patterns of NOSs expression may have different biological functions. Therefore, we hypothesized that tendon overuse may result in a differential upregulation of NOSs, particularly iNOS. An animal model of supraspinatus tendon overuse was utilized, which consisted of treadmill running. A group of animals of the same strain and age subjected to normal cage activity were used as controls. Following a 4-week exercise protocol supraspinatus tendons were harvested, RNA was extracted, and subjected to competitive reverse transcription and polymerase chain reaction (RT-PCR) to determine the expression levels of inducible-, endothelial-, and neuronal-NOS isoforms (i-, e-, and nNOS). The mRNA expression of all three NOS isoforms increased in the supraspinatus tendons as a result of overuse exercise. iNOS and eNOS mRNA expression increased fourfold ( p < 0.01), and there was an increase, but statistically not significant, in nNOS mRNA expression in the overused tendons when compared with the controls. This study is the first to show that NOS isoforms are upregulated in rotator cuff tendon as a result of chronic overuse, and suggests the involvement of nitric oxide in the response of tendon tissue to increased mechanical stress. ß

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Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism.

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Cited by 177 publications

References 40 publications

Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

Permissive Role of Nitric Oxide in Endothelin-induced Migration of Endothelial Cells

Overexpression of nitric oxide synthases in tendon overuse

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